*2.1. Study Population*

A total of 83 cases were recruited at the Department of Internal Medicine, Fondazione I.R.C.C.S. Policlinico San Matteo (Pavia, Italy) from November 1st, 2015 to June 30th, 2018. They included 52 CD patients, comprehensive of all the possible combinations of diet and villous atrophy (Table 1), i.e., 13 ACD, 29 TCD, 4 RCD, 6 PCD, and 31 patients with functional dyspepsia [7] who served as controls (C). The demographic and clinical features of all recruited cases are shown in Table 2. No significant differences regarding age and comorbidities were found among the groups, albeit the statistical analysis was not performed with the potential and refractory ones due to the small sample size. Diagnoses of PCD, ACD, TCD, and RCD were made on the basis of widely accepted criteria [8] and histological examination of mucosal lesions [9]. The adherence to gluten-free diet (GFD) was evaluated by means of a five-level score, with scores ranging 0 to 2 meaning absence or poor adherence and scores ranging 3 to 4 being indicative of good adherence [10]. Moreover, all enrolled cases followed a Mediterranean diet, and there were no vegan/vegetarian patients.




**Table 2.** Demographic and clinical features of study cohort.

Abbreviations: GFD: gluten-free diet; HLA: Human Leukocyte Antigen; +ve: positive; −ve: negative.

Patients were excluded if they had recent (within 4 weeks) or current use of medications that could affect bowel function and/or microbiota composition, such as antibiotics, prebiotics, probiotics, opioids, nonsteroidal anti-inflammatory drugs, proton pump inhibitors, laxatives, steroids, or antidiarrheal drugs.

The protocol was approved by the local Ethics Committee (protocol number 20150003822), and each enrolled case gave written informed consent.

### *2.2. Biological Samples*
